Effects of grapefruit juice on the absorption of levothyroxine
Open accessAbstract
AIMS: Our aim was to study the effect of grapefruit juice on the pharmacokinetics of levothyroxine. METHODS: In a randomized cross-over study with two phases, 10 healthy subjects ingested 200 ml grapefruit juice or water (control) three times daily for 2 days. On day 3, a single 600 microg dose of levothyroxine was administered with 200 ml grapefruit juice or water, which was also ingested 1 h before and 1 h after levothyroxine. Serum concentrations of total thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured up to 24 h. RESULTS: Grapefruit juice decreased slightly (11%; P < 0.01) the maximal increase of T4 concentration after ingestion of levothyroxine from 66.4 nmol l(-1) to 59.4 nmol l(-1) (95% CI on the difference -11.3, -2.7). The incremental areas under the serum T4 concentration-time curve (dAUC) during the first 4 and 6 h were also decreased slightly: dAUC(0,4 h) by 13% (P < 0.05), from 195 nmol l(-1) h to 169 nmol l(-1) h (95% CI -51, -1) and dAUC(0,6 h) by 9% (P = 0.085), from 298 nmol l(-1) h to 271 nmol l(-1) h (95% CI -58, 4). The decrease in the serum concentration of TSH (1.25 mU l(-1)) measured 24 h after ingestion of levothyroxine, was not altered by grapefruit juice. CONCLUSIONS: Grapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability. Accordingly, the clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some ingredients of natural juices, particularly grapefruit and apple juice, may block OATP, MCT, or NTCP carrying LT4 from small intestine to circulation.
“Some ingredients of natural juices, particularly grapefruit and apple juice, may block the organic anion-transporting polypeptide (OATP) family and the monocarboxylate transporter (MCT) family or NTCP (sodium–taurocholate co-transporting polypeptide) carrying LT4 from the small intestine to the circulation (59).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [59]
The Introduction says levothyroxine absorption may involve OATP transporters, and the Discussion speculates that grapefruit juice could inhibit transporters important to absorption in some individuals. But the Discussion says this study's results suggest grapefruit juice does not interfere with those transporters; our copy provides no support for apple juice or for MCT or NTCP inhibition of levothyroxine uptake. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSome drugs (eg, ciprofloxacin, rifampicin, and chromium picolinate) and grapefruit juice alter intestinal mucosal transporters, including the monocarboxylate transporter family and organic anion transporting polypeptides.
“In addition, some drugs (eg, ciprofloxacin, rifampicin, and chromium picolinate) and grapefruit juice alter intestinal mucosal transporters, including the monocarboxylate transporter family and organic anion transporting polypeptides (81–83).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [82]
Grapefruit juice taken 1 hour before or after levothyroxine lowers its bioavailability by delaying absorption.
“Additionally, consuming grapefruit juice 1 h before or after LT4 ingestion decreases its bioavailability by delaying its absorption.50”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [50]
TSH levels did not appear to be affected by concomitant grapefruit juice and LT4 intake, and investigators considered it not clinically relevant.
“However, TSH levels did not appear to be affected, and the investigators considered that concomitant grapefruit juice and LT4 intake did not have a clinically relevant effect [ 82 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [82]
Taking LT4 with grapefruit juice was associated with statistically significant decreases (around 10%) in peak T4 concentration and AUC for T4.
“Taking LT4 with grapefruit juice was associated with statistically significant decreases (of around 10%) in the peak T4 concentration and the AUC for T4.”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [82]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Grapefruit juice–drug interactions
Bailey, D. G., Malcolm, J., Arnold, O., & Spence, J. D. (1998) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1998.00764.x · Cited by 751 · see citing works
Lown, K. S., Bailey, D. G., Fontana, R. J., Janardan, S. K., Adair, C. H., Fortlage, L. A., Brown, M. B., Guo, W., & Watkins, P. B. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119439 · Cited by 624 · see citing works
Dresser, G. K., Bailey, D. G., Leake, B. F., Schwarz, U. I., Dawson, P. A., Freeman, D. J., & Kim, R. B. (2002) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2002.121152 · Cited by 606 · see citing works
Interaction of citrus juices with felodipine and nifedipine
Bailey, D., Spence, J. D., Munoz, C., & Arnold, J. M. O. (1991) · The Lancet · doi:10.1016/0140-6736(91)90872-m · Cited by 596 · see citing works
Disposition of intravenous and oral cyclosporine after administration with grapefruit juice*
Ducharme, M. P., Warbasse, L. H., & Edwards, D. J. (1995) · Clinical Pharmacology & Therapeutics · doi:10.1016/0009-9236(95)90032-2 · Cited by 349 · see citing works
Lilja, J. J., Kivistö, K. T., & Neuvonen, P. J. (1998) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(98)90130-8 · Cited by 313 · see citing works
Self-citationFerrous sulfate reduces thyroxine efficacy in patients with hypothyroidism
Campbell, N. R. C., Hasinoff, B. B., Stalts, H., Rao, B., & Wong, N. C. W. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-12-1010 · Cited by 231 · see citing works
Transporters and Renal Drug Elimination
Lee, W., & Kim, R. B. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121856 · Cited by 222 · see citing works
Fujiwara, K., Adachi, H., Nishio, T., Unno, M., Tokui, T., Okabe, M., Onogawa, T., Suzuki, T., Asano, N., Tanemoto, M., et al. (2001) · Endocrinology · doi:10.1210/endo.142.5.8115 · Cited by 188 · see citing works
The influence of cholestyramine on thyroxine absorption
Northcutt, R. C. (1969) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1969.03160100047012 · Cited by 144 · see citing works
Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol
Lilja, J. J., Backman, J. T., Laitila, J., et al. (2003) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2003.26 · Cited by 141 · see citing works
Self-citationLiel, Y., Harman-Boehm, I., & Shany, S. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.2.8636317 · Cited by 129 · see citing works
Grapefruit juice‐drug interactions
Bailey, D. G., Arnold, J. M. O., & Spence, J. D. (2004) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2004.02305.x · Cited by 127 · see citing works
Sucralfate causes malabsorption of L-thyroxine
Sherman, S. I., Tielens, E. T., & Ladenson, P. W. (1994) · The American Journal of Medicine · doi:10.1016/0002-9343(94)90093-0 · Cited by 105 · see citing works
Nonspecific intestinal adsorption of levothyroxine by aluminum hydroxide
Liel, Y., Sperber, A. D., & Shany, S. (1994) · The American Journal of Medicine · doi:10.1016/0002-9343(94)90303-4 · Cited by 83 · see citing works
Effects of Pharmacological Fiber Supplements on Levothyroxine Absorption
Chiu, A. C., & Sherman, S. I. (1998) · Thyroid® · doi:10.1089/thy.1998.8.667 · Cited by 41 · see citing works
ABSORPTION AND MALABSORPTION OF LEVOTHYROXINE SODIUM
Sherman, S. I., & Malecha, S. E. (1995) · American Journal of Therapeutics · doi:10.1097/00045391-199510000-00014 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
Timing of levothyroxine administration affects serum thyrotropin concentration
Bach-Huynh, T.-G., Nayak, B., Loh, J., Soldin, S., & Jonklaas, J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0860 · Cited by 198 · see citing works
A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism
Colucci, P., Yue, C. S., Ducharme, M., Benvenga, S., Principal Scientist, L. A. C. I., Principal Scientist, L. A. C. I. A. P. C., President and CEO, L. A. C. I., & Professor of Medicine, D. (2010) · European Endocrinology · doi:10.17925/ee.2013.09.01.40 · Cited by 167 · see citing works
Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164 · see citing works
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.005 · Cited by 133 · see citing works
Vita, R., Saraceno, G., Trimarchi, F., & Benvenga, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2684 · Cited by 99 · see citing works
Levothyroxine interactions with food and dietary supplements – a systematic review
Wiesner, A., Gajewska, D., & Paśko, P. (2021) · Pharmaceuticals · doi:10.3390/ph14030206 · Cited by 85 · see citing works
“[69] reported a case of a 36-year-old hypothyroid woman, successfully treated with L-T4 (100 μg daily).”
BackgroundInfluentialWhen thyroid hormone replacement is ineffective?
Benvenga, S. (2013) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000003 · Cited by 74 · see citing works
Walker, J. N., Shillo, P., Ibbotson, V, Vincent, A., Karavitaki, N., Weetman, A. P., Wass, J. A. H., & Allahabadia, A. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-1035 · Cited by 70 · see citing works
Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast
Perez, C. L. S., Araki, F. S., Graf, H., & de Carvalho, G. A. (2013) · Thyroid · doi:10.1089/thy.2012.0435 · Cited by 63 · see citing works
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Asik, M., Gunes, F., Binnetoglu, E., Eroglu, M., Bozkurt, N., Sen, H., Akbal, E., Bakar, C., Beyazit, Y., & Ukinc, K. (2014) · Endocrine · doi:10.1007/s12020-013-0065-1 · Cited by 58 · see citing works
Caron, P., Grunenwald, S., Persani, L., Borson-Chazot, F., Leroy, R., & Duntas, L. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09691-9 · Cited by 53 · see citing works
Ward, L. S. (2010) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302010000500002 · Cited by 53 · see citing works
Rostami, E., Kashanian, S., & Azandaryani, A. H. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3216-4 · Cited by 40 · see citing works
Centanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38 · see citing works
“…of natural juices, particularly grapefruit and apple juice, may block the organic anion-transporting polypeptide (OATP) family and the monocarboxylate transporter (MCT) family or NTCP (sodium – taurocholate co-transporting polypeptide) carrying LT4 from the small intestine to the circulation (59).”
Tanguay, M., Girard, J., Scarsi, C., Mautone, G., & Larouche, R. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.608 · Cited by 33 · see citing works
Bernareggi, A., Grata, E., Pinorini, M., & Conti, A. (2013) · Pharmaceutics · doi:10.3390/pharmaceutics5040621 · Cited by 30 · see citing works
The clinical utility of free thyroxine in oral levothyroxine absorption testing
Ching Sun, G. E., Pantalone, K. M., Faiman, C., Gupta, M., Olansky, L., & Hatipoglu, B. (2014) · Endocrine Practice · doi:10.4158/ep13487.or · Cited by 27 · see citing works
PEG-stearate coated solid lipid nanoparticles as levothyroxine carriers for oral administration
Kashanian, S., & Rostami, E. (2014) · Journal of Nanoparticle Research · doi:10.1007/s11051-014-2293-6 · Cited by 28 · see citing works
Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
Liu, H., Lu, M., Hu, J., Fu, G., Feng, Q., Sun, S., & Chen, C. (2023) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s414460 · Cited by 29 · see citing works
Ciprofloxacin and Rifampin have opposite effects on levothyroxine absorption
Goldberg, A. S., Tirona, R. G., Asher, L. J., Kim, R. B., & Van Uum, S. H. M. (2013) · Thyroid · doi:10.1089/thy.2013.0014 · Cited by 25 · see citing works
Lombardi, C. P., Bocale, R., Barini, A., Barini, A., D’Amore, A., Boscherini, M., & Bellantone, R. (2017) · Endocrine · doi:10.1007/s12020-016-1003-9 · Cited by 23 · see citing works
The use of levothyroxine absorption tests in clinical practice
Caron, P., & Declèves, X. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad132 · Cited by 18 · see citing works
Refractory hypothyroidism: unraveling the complexities of diagnosis and management
Quiroz-Aldave, J. E., Concepción-Zavaleta, M. J., Durand-Vásquez, M. D. C., Concepción-Urteaga, L. A., Gamarra-Osorio, E. R., Suárez-Rojas, J., Rafael-Robles, L. D. P., Paz-Ibarra, J., & Román-González, A. (2023) · Endocrine Practice · doi:10.1016/j.eprac.2023.09.003 · Cited by 14 · see citing works
- Authors
- Lilja, J. J., Laitinen, K., & Neuvonen, P. J.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Lilja, Jari J.
- ORCID
- Neuvonen, Pertti J.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2005-05-31
- Volume
- 60
- Issue
- 3
- Pages
- 337-341
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1884777
- OpenAlex
- W2032069645
- Cited by
- 74
- References
- 17
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 1 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- grapefruit juice, levothyroxine, drug-drug interactions, pharmacokinetics, bioavailability, thyroxine, thyroid-stimulating hormone, absorption, antithyroid drugs
- MeSH terms
- Adult, Beverages, Biological Availability, Citrus, Female, Humans, Intestinal Absorption, Male, Thyroxine, Food-Drug Interactions, Cross-Over Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
